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PMC:7696151 / 72712-75833 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
2157 791-795 Gene denotes P-gp Gene:283871
2158 797-802 Gene denotes ABCB1 Gene:5243
2159 1587-1591 Gene denotes KRAS Gene:16653
2160 1617-1620 Gene denotes p53 Gene:22060
2161 1764-1767 Gene denotes p53 Gene:22060
2162 1931-1934 Gene denotes p53 Gene:22060
2163 1960-1963 Gene denotes p53 Gene:22060
2164 2384-2387 Gene denotes p53 Gene:22060
2165 2549-2552 Gene denotes p53 Gene:22060
2166 2621-2625 Gene denotes KRAS Gene:16653
2167 1415-1421 Species denotes murine Tax:10090
2168 1551-1555 Species denotes Mice Tax:10090
2169 2591-2595 Species denotes mice Tax:10090
2170 0-3 Chemical denotes HCQ MESH:D006886
2171 80-83 Chemical denotes HCQ MESH:D006886
2172 746-749 Chemical denotes HCQ MESH:D006886
2173 1147-1150 Chemical denotes HCQ MESH:D006886
2174 1696-1699 Chemical denotes HCQ MESH:D006886
2175 1800-1803 Chemical denotes HCQ MESH:D006886
2176 2152-2155 Chemical denotes HCQ MESH:D006886
2177 2281-2284 Chemical denotes HCQ MESH:D006886
2178 2782-2792 Chemical denotes trametinib MESH:C560077
2179 2953-2956 Chemical denotes HCQ MESH:D006886
2180 2980-2990 Chemical denotes trametinib MESH:C560077
2181 162-168 Disease denotes tumors MESH:D009369
2182 525-531 Disease denotes cancer MESH:D009369
2183 881-893 Disease denotes cytotoxicity MESH:D064420
2184 897-915 Disease denotes refractory cancers MESH:D009369
2185 991-997 Disease denotes cancer MESH:D009369
2186 1043-1048 Disease denotes tumor MESH:D009369
2187 1365-1370 Disease denotes tumor MESH:D009369
2188 1432-1464 Disease denotes pancreatic ductal adenocarcinoma MESH:D021441
2189 1476-1482 Disease denotes cancer MESH:D009369
2190 1495-1504 Disease denotes mortality MESH:D003643
2191 1673-1678 Disease denotes tumor MESH:D009369
2192 1818-1823 Disease denotes tumor MESH:D009369
2193 1984-1990 Disease denotes cancer MESH:D009369
2194 2042-2075 Disease denotes pancreatic ductal adenocarcinomas MESH:D021441
2195 2167-2172 Disease denotes tumor MESH:D009369
2196 2323-2355 Disease denotes pancreatic ductal adenocarcinoma MESH:D021441
2197 2693-2718 Disease denotes pancreatic carcinogenesis MESH:D063646
2198 3036-3061 Disease denotes reduction of tumor lesion MESH:D051437
2199 3080-3085 Disease denotes tumor MESH:D009369
2200 3098-3104 Disease denotes cancer MESH:D009369
2201 3116-3120 Disease denotes pain MESH:D010146

LitCovid-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T135 525-531 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664
T136 614-629 Phenotype denotes drug resistance http://purl.obolibrary.org/obo/HP_0020174
T137 991-997 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664
T138 1043-1048 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T139 1365-1370 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T140 1476-1482 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664
T141 1673-1678 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T142 1818-1823 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T143 1984-1990 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664
T144 2167-2172 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T145 3049-3054 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T146 3080-3085 Phenotype denotes tumor http://purl.obolibrary.org/obo/HP_0002664
T147 3098-3104 Phenotype denotes cancer http://purl.obolibrary.org/obo/HP_0002664
T148 3116-3120 Phenotype denotes pain http://purl.obolibrary.org/obo/HP_0012531

LitCovid-sentences

Id Subject Object Predicate Lexical cue
T465 0-79 Sentence denotes HCQ explains its antitumor activity thanks to its ability to inhibit autophagy.
T466 80-144 Sentence denotes HCQ is, indeed, an FDA-approved drug inhibiting autophagy [135].
T467 145-222 Sentence denotes Several types of tumors develop chemoresistance by enhancing autophagic flux.
T468 223-405 Sentence denotes Autophagy consists in the sequestration of materials in autophagic vesicles to be eliminated through lysosomal fusion and allows cells to overcome metabolic and therapeutic stresses.
T469 406-508 Sentence denotes By recycling intracellular components, cells may maintain an energy balance and increase their growth.
T470 509-575 Sentence denotes If it occurs in cancer cells, resistance mechanisms may establish.
T471 576-719 Sentence denotes One of the mechanisms responsible for drug resistance is related to increased drug efflux by ATP-binding cassette (ABC) transporters [136,137].
T472 720-956 Sentence denotes It has been observed that HCQ is significantly reduced the increase in P-gp (ABCB1) expression and, in combination with several anticancer drugs, induced higher cytotoxicity in refractory cancers by inhibiting autophagic activity [138].
T473 957-1073 Sentence denotes However, the role of autophagy in cancer is controversial and depends on genotype and tumor stage development [139].
T474 1074-1271 Sentence denotes Many clinical trials examined the synergistic effects of the addition of HCQ to conventional chemotherapic drugs, finding that the role of autophagy is complex and is influenced by several factors.
T475 1272-1389 Sentence denotes Depending on genetic concomitant alterations, autophagy may possess both pro-tumorigenic and tumor-suppressive roles.
T476 1390-1550 Sentence denotes It has been confirmed in murine models of pancreatic ductal adenocarcinoma, a type of cancer with a high mortality rate, due to its refractoriness to therapies.
T477 1551-1720 Sentence denotes Mice presenting activated oncogenic KRAS and normal expression of p53 oncosuppressor experienced a critical regression of tumor developing under HCQ (60 mg/kg/day i.p.).
T478 1721-1941 Sentence denotes By contrast, in those with a deficiency of p53, the inhibition of autophagy by HCQ increased the tumor progression, demonstrating that autophagy’s role in tumorigenesis is strictly related to the expression of p53 [140].
T479 1942-2082 Sentence denotes The expression of p53 is often altered in cancer, so as to be found mutated or absent in the 75% of pancreatic ductal adenocarcinomas [141].
T480 2083-2179 Sentence denotes This issue highlights the necessity to carefully evaluate the use of HCQ in certain tumor types.
T481 2180-2405 Sentence denotes Different outcomes have been previously described, it has been found that inhibition of autophagy by HCQ might arise as a valuable adjuvant in pancreatic ductal adenocarcinoma chemotherapy, regardless of p53 status [142,143].
T482 2406-2610 Sentence denotes Given the same doses and route of administration, these inconsistencies between the two reported studies could probably derive from the use of p53 homozygous and heterozygous models of mice, respectively.
T483 2611-2719 Sentence denotes Regarding KRAS oncoprotein, its downstream pathway is one of the major players of pancreatic carcinogenesis.
T484 2720-2844 Sentence denotes The inhibition of this pathway by cytotoxic drugs, as well as trametinib, is often associated with an increase in autophagy.
T485 2845-3121 Sentence denotes For this reason, Drucker and Rosen [144] performed an off-label trial with an association of 400–1200 mg of HCQ and a constant dose of trametinib, observing a partial response with a general reduction of tumor lesion size, circulating tumor markers and cancer-associated pain.